Physiological basis of tingling paresthesia evoked by hydroxy-alpha-sanshool

J Neurosci. 2010 Mar 24;30(12):4353-61. doi: 10.1523/JNEUROSCI.4666-09.2010.

Abstract

Hydroxy-alpha-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-alpha-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultrasensitive light-touch receptors in the skin and targets novel populations of Abeta and C fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Amides
  • Animals
  • Animals, Newborn
  • Capsaicin / pharmacology
  • Cells, Cultured
  • In Vitro Techniques
  • Isoquinolines / pharmacology
  • Mechanoreceptors / drug effects
  • Mechanoreceptors / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mustard Plant
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology
  • Nerve Growth Factors / pharmacology
  • Neural Conduction / drug effects
  • Neural Conduction / physiology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology*
  • Paresthesia / chemically induced*
  • Paresthesia / pathology*
  • Paresthesia / physiopathology
  • Plant Oils / pharmacology
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology
  • Sensory System Agents / pharmacology
  • Skin / innervation*
  • Statistics, Nonparametric
  • Touch / physiology
  • Trigeminal Ganglion / cytology
  • Urea / analogs & derivatives
  • Urea / pharmacology
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • 1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea
  • Amides
  • Isoquinolines
  • Nerve Growth Factors
  • Plant Oils
  • Sensory System Agents
  • sanshool
  • gamma-Aminobutyric Acid
  • Urea
  • neurotrophin 4
  • Capsaicin
  • mustard oil